R43AG084372
Project Grant
Overview
Grant Description
Estrogen receptor reprogramming ligands for the prevention of protracted menopausal symptoms and chronic diseases - project summary/abstract.
Because of longer lifespans, health problems affecting menopausal women are becoming increasingly common. Hot flashes, sleep issues, and mood swings are typical short-term symptoms that can have a negative impact on quality of life and productivity at work.
An increased incidence of chronic disorders such as osteoporosis, obesity, diabetes, metabolic syndrome, and cardiovascular disease is linked to long-term estrogen insufficiency following menopause. Menopausal hormone therapy (MHT) is effective at reducing menopausal symptoms and preventing some chronic diseases, but according to the Women's Health Initiative (WHI), long-term therapy has more risks than benefits.
The use of MHT among menopausal women has sharply dropped since the publication of the WHI data. MHT is currently recommended for a 5-year short-term treatment of hot flashes and vaginal symptoms. MHT is no longer recommended for the primary prevention of chronic diseases.
Countless menopausal women continue to wait anxiously for a safer long-term MHT to improve their quality of life and health. In the meantime, many women opt for unproven supplements to relieve menopausal symptoms.
There is a significant unmet need for developing new MHT formulations that can be utilized for long-term therapy because many women suffer from menopausal symptoms for more than five years and chronic diseases increase throughout menopause.
Almost 80 years after MHT was approved, there is still no MHT formula safe for long-term therapy. Our objective is to develop a safer MHT formula that can be used long-term to treat protracted menopausal symptoms and prevent chronic diseases, such as osteoporosis, diabetes, obesity, and metabolic syndrome.
We discovered a class of compounds that we termed estrogen receptor (ER) reprogramming ligands. We found that when a reprogramming ligand is combined with estradiol (E2), a new set of genes are regulated that are not regulated by the reprogramming ligand or E2 alone.
The reprogramming ligand blocked the proliferation of human breast cancer cells and the growth of the mouse uterus in response to E2. Our goal is to create an E2/reprogramming ligand combination by replacing the progestin component of MHT with a reprogramming ligand and adding it to the estrogen-alone formulation.
Our hypothesis is that the E2/reprogramming ligand combination will be safer than the single estrogen and estrogen/progestin MHT preparations currently on the market so that they can be used as a long-term therapy to prevent protracted menopausal symptoms and chronic diseases.
Our original reprogramming ligand was a natural compound. To improve its pharmacological properties and strengthen its patent protection, we prepared and identified several synthetic analogs that behave similarly to the natural reprogramming ligand in cell-based assays.
As the next step in the clinical development pathway, we will test the synthetic analogs in animal models to select the lead analog that is the most effective and safe for future clinical trials.
Because of longer lifespans, health problems affecting menopausal women are becoming increasingly common. Hot flashes, sleep issues, and mood swings are typical short-term symptoms that can have a negative impact on quality of life and productivity at work.
An increased incidence of chronic disorders such as osteoporosis, obesity, diabetes, metabolic syndrome, and cardiovascular disease is linked to long-term estrogen insufficiency following menopause. Menopausal hormone therapy (MHT) is effective at reducing menopausal symptoms and preventing some chronic diseases, but according to the Women's Health Initiative (WHI), long-term therapy has more risks than benefits.
The use of MHT among menopausal women has sharply dropped since the publication of the WHI data. MHT is currently recommended for a 5-year short-term treatment of hot flashes and vaginal symptoms. MHT is no longer recommended for the primary prevention of chronic diseases.
Countless menopausal women continue to wait anxiously for a safer long-term MHT to improve their quality of life and health. In the meantime, many women opt for unproven supplements to relieve menopausal symptoms.
There is a significant unmet need for developing new MHT formulations that can be utilized for long-term therapy because many women suffer from menopausal symptoms for more than five years and chronic diseases increase throughout menopause.
Almost 80 years after MHT was approved, there is still no MHT formula safe for long-term therapy. Our objective is to develop a safer MHT formula that can be used long-term to treat protracted menopausal symptoms and prevent chronic diseases, such as osteoporosis, diabetes, obesity, and metabolic syndrome.
We discovered a class of compounds that we termed estrogen receptor (ER) reprogramming ligands. We found that when a reprogramming ligand is combined with estradiol (E2), a new set of genes are regulated that are not regulated by the reprogramming ligand or E2 alone.
The reprogramming ligand blocked the proliferation of human breast cancer cells and the growth of the mouse uterus in response to E2. Our goal is to create an E2/reprogramming ligand combination by replacing the progestin component of MHT with a reprogramming ligand and adding it to the estrogen-alone formulation.
Our hypothesis is that the E2/reprogramming ligand combination will be safer than the single estrogen and estrogen/progestin MHT preparations currently on the market so that they can be used as a long-term therapy to prevent protracted menopausal symptoms and chronic diseases.
Our original reprogramming ligand was a natural compound. To improve its pharmacological properties and strengthen its patent protection, we prepared and identified several synthetic analogs that behave similarly to the natural reprogramming ligand in cell-based assays.
As the next step in the clinical development pathway, we will test the synthetic analogs in animal models to select the lead analog that is the most effective and safe for future clinical trials.
Awardee
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
San Francisco,
California
94107
United States
Geographic Scope
Single Zip Code
Iaterion was awarded
Project Grant R43AG084372
worth $298,883
from National Institute on Aging in September 2023 with work to be completed primarily in San Francisco California United States.
The grant
has a duration of 1 year and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity PHS 2022-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed).
SBIR Details
Research Type
SBIR Phase I
Title
Estrogen receptor reprogramming ligands for the prevention of protracted menopausal symptoms and chronic diseases
Abstract
Project Summary/Abstract Because of longer lifespans, health problems affecting menopausal women are becoming increasingly common. Hot flashes, sleep issues, and mood swings are typical short-term symptoms that can have a negative impact on quality of life and productivity at work. An increased incidence of chronic disorders such as osteoporosis, obesity, diabetes, metabolic syndrome, and cardiovascular disease is linked to long-term estrogen insufficiency following menopause. Menopausal hormone therapy (MHT) is effective at reducing menopausal symptoms and preventing some chronic diseases, but according to the Women's Health Initiative (WHI), long-term therapy has more risks than benefits. The use of MHT among menopausal women has sharply dropped since the publication of the WHI data. MHT is currently recommended for a 5-year short-term treatment of hot flashes and vaginal symptoms. MHT is no longer recommended for the primary prevention of chronic diseases. Countless menopausal women continue to wait anxiously for a safer long-term MHT to improve their quality of life and health. In the meantime, many women opt for unproven supplements to relieve menopausal symptoms. There is a significant unmet need for developing new MHT formulations that can be utilized for long-term therapy because many women suffer from menopausal symptoms for more than five years and chronic diseases increase throughout menopause. Almost 80 years after MHT was approved, there is still no MHT formula safe for long- term therapy. Our objective is to develop a safer MHT formula that can be used long-term to treat protracted menopausal symptoms and prevent chronic diseases, such as osteoporosis, diabetes, obesity, and metabolic syndrome. We discovered a class of compounds that we termed estrogen receptor (ER) reprogramming ligands. We found that when a reprogramming ligand is combined with estradiol (E2), a new set of genes are regulated that are not regulated by the reprogramming ligand or E2 alone. The reprogramming ligand blocked the proliferation of human breast cancer cells and the growth of the mouse uterus in response to E2. Our goal is to create an E2/reprogramming ligand combination by replacing the progestin component of MHT with a reprogramming ligand and adding it to the estrogen-alone formulation. Our hypothesis is that the E2/reprogramming ligand combination will be safer than the single estrogen and estrogen/progestin MHT preparations currently on the market so that they can be used as a long-term therapy to prevent protracted menopausal symptoms and chronic diseases. Our original reprogramming ligand was a natural compound. To improve its pharmacological properties and strengthen its patent protection, we prepared and identified several synthetic analogs that behave similarly to the natural reprogramming ligand in cell-based assays. As the next step in the clinical development pathway, we will test the synthetic analogs in animal models to select the lead analog that is the most effective and safe for future clinical trials.
Topic Code
R
Solicitation Number
PA22-176
Status
(Complete)
Last Modified 9/5/23
Period of Performance
9/1/23
Start Date
8/31/24
End Date
Funding Split
$298.9K
Federal Obligation
$0.0
Non-Federal Obligation
$298.9K
Total Obligated
Activity Timeline
Additional Detail
Award ID FAIN
R43AG084372
SAI Number
R43AG084372-3435681056
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Small Business
Awarding Office
75NN00 NIH NATIONAL INSITUTE ON AGING
Funding Office
75NN00 NIH NATIONAL INSITUTE ON AGING
Awardee UEI
KEGPJGAUS5K3
Awardee CAGE
7FY34
Performance District
CA-11
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute on Aging, National Institutes of Health, Health and Human Services (075-0843) | Health research and training | Grants, subsidies, and contributions (41.0) | $298,883 | 100% |
Modified: 9/5/23